Functional understanding of the human gut microbiota remains hampered by a lack of cultured isolates. Here, we report on two isolates recovered from the stool of a healthy pre-adolescent child that are closely related to Flavonifractor plautii (strain SP1) and Pseudoflavonifractor capillosus (strain SP2). Both species are representative members of Clostridium cluster IV and have been implicated with polyphenol metabolism, but are still poorly characterized from a genomic and biochemical perspective. Cultures of F. plautii SP1 and DSMZ 4000T both rapidly degrade the model polyphenol quercetin, but active growth of both strains is conditional on its complete degradation. The F. plautii strains including SP1 show a high degree of genome synteny, size (~4.6 Mbp) and GC content (~60%). All strains possess a chalcone isomerase (Chi) that is involved in the taxipholin-alphitonin conversion central to quercetin degradation, and resides within a multi-gene locus that is conserved across all these strains. Interestingly, both the F. plautii 16S rRNA gene and the genes from the putative chi-containing operon are significantly more abundant in the metagenomic data for Crohn’s disease patients compared to healthy controls available on the online annotation server MetaQuery. Both strain SP2 and Pf. capillosus DSMZ 23940T are unable to degrade quercetin, and their yield is slightly reduced in its presence. However, while the 16S rRNA phylogeny suggests they are closely related, the SP2 genome possesses only a small amount of synteny and is much smaller with a lower GC content (~56%) than the P. capillosus and other Pseudoflavonifractor spp. genomes. Core genome phylogeny and Average Nucleotide Identity scores show that strain SP2 instead is the first cultured isolate of three “uncultured_Clostridium/Flavonifractor” metagenome-assembled genomes. Collectively, these studies expand our understanding of the functional attributes of a numerically predominant but poorly characterized component of the core microbiome of the human gut, and their links with diet, digestive function and health.